Sialidase-like Asp-boxes: Sequence-similar structures within different protein folds

Sequence similarity is the most common measure currently used to infer homo logy between proteins. Typically, homologous protein domains show sequence similarity over their entire lengths. Here we identify Asp box motifs, init ially found as repeats in sialidases and neuraminidases, in new structural and sequence contexts. These motifs represent significantly similar sequenc es, localized to P hairpins within proteins that are otherwise different in sequence and three-dimensional structure. By performing a combined sequenc e-and structure-based analysis we detect Asp boxes in more than nine protei n families, including bacterial ribonucleases, sulfite oxidases, reelin, ne trins, some lipoprotein receptors, and a variety of glycosyl hydrolases. Al though the function common to each of these proteins, if any, remains uncle ar, we discuss possible functions of Asp boxes on the basis of previously d etermined experimental results and discuss different evolutionary scenarios for the origin of Asp-box containing proteins.